DESCRIPTION: (Adapted from the application abstract) Using a strain of feline immunodeficiency virus (FIV) that induces rapid disease, the applicant will examine whether a cytokine profile switch from a Type 1 to a Type 2 response occurs during progression to AIDS and, if so, how this change relates to the immunopathology associated with the virus. Aim 1 will focus on the patterns of cytokine production (Type 1 versus Type 2) from the time of initial viral replication through progression to clinical illness. Aim 2 will use the model developed in Aim 1 to study the effect of early treatment with IL-12, a potent Type 1 cytokine in the host's ability to control viral replication and resist disease induction. a. Candidate: Dr. Avery received his VMD in 1991 from Cornell University. He worked for 2 years in practice, then worked as a Research Fellow in Dr. Finberg's laboratory. Dr. Avery lists one publication from work in Dr. Finberg's laboratory and a manuscript in preparation. b. Mentor: Dr. Edward Hoover is a Professor in the Department of Pathology at Colorado State University. He has mentored 18 Ph.D. and postdoctoral students. His laboratory has developed the key systems that will be used in this project. Dr. Hoover has R01 and N01 grants to study FIV pathogenesis and to use the FIV model for evaluation of therapeutic approaches. c. Career Development Plan: Coursework is included in the career development plan which will provide the candidate with the background in virology, molecular biology, biochemistry and immunology that will be necessary for this project and for a career in infectious disease/AIDS research. d. Research Plan: Studies are proposed to utilize an accelerated FIV/cat infection model employing a highly virulent strain of virus which induces rapid immunodeficiency disease and a corresponding high viral burden. This rapid disease progression model will be used to examine potential perturbances in the patterns of TH1-like and TH2-like cytokine expression which may accompany infection and progression to a fatal outcome. An Advisory Committee is available to guide and review the candidate's research progress. e. Environment and Institutional Commitment: The proposed research will be performed in Dr. Hoover's laboratory in the Department of Pathology at Colorado State University.